tbuckley/cabot-search huggingface dataset:
SPADE: Design of a real-world observational study of avelumab first-line (1L) maintenance in advanced urothelial carcinoma (UC) in the Asia-Pacific (APAC) region.
Authors: Po-Jung Su, Se Hoon Park, Yu Chieh Tsai, Miso Kim, Wen-Jeng Wu, Seasea Gao, Sang Joon Shin
Journal: Journal of Clinical Oncology (2023)

TPS577 Background: UC is a common cancer, with &gt;200,000 new cases reported in the APAC region in 2020. In the global phase 3 JAVELIN Bladder 100 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in patients with advanced UC that had not progressed with 1L platinum-containing chemotherapy (median OS, 23.8 vs 15.0 months [p=0.0036]; median PFS, 5.5 vs 2.1 months [p&lt;0.0001]), leading to regulatory approvals worldwide and incorporation into international treatment guidelines with level 1 evidence. The objectives of the SPADE noninterventional study are to evaluate real-world patient characteristics, treatment patterns, patient-reported outcomes (PROs) and treatment outcomes with avelumab maintenance administered in patients with advanced UC without disease progression after 1L platinum-based chemotherapy in the APAC region. Methods: SPADE is a multicenter, prospective, observational study ongoing in Australia, Hong Kong, India, Japan, Republic of Korea, Singapore, Taiwan, and other countries. Overall, 286 patients with unresectable locally advanced or metastatic (stage IV) measurable UC of any histology that has not progressed with 1L platinum-containing chemotherapy, for whom avelumab 1L maintenance therapy is planned, will be enrolled. All patients will receive avelumab 800 mg intravenously every 2 weeks (or per local marketing authorization) and will be followed up for 12 months or until avelumab is discontinued. The decision to start avelumab treatment should be made in advance by the treating physician and per local clinical practice. Data collected will include patient demographics (ECOG performance status, renal function, history of UC, primary tumor location, location of metastases, and prior therapy), treatment details for 1L platinum-based chemotherapy (regimen, cycles, and response per RECIST), treatment details for avelumab 1L maintenance (interval from end of chemotherapy until initiation, duration of avelumab treatment, and planned subsequent treatment), and treatment outcomes with avelumab 1L maintenance (6- and 12-month OS and health-related quality of life). Data sources will include medical records collected during routine clinical care. Data for baseline treatment patterns will be summarized using descriptive statistics. OS will be analyzed using the Kaplan-Meier method. Health-related quality of life, including changes over time, will be measured using the EQ-5D-5L and National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index (NCCN/FACT FBISI-18) questionnaires. An interim analysis is planned after ~30% of patients have been enrolled.
Impact of neoadjuvant chemotherapy–induced acute kidney injury on oncological outcomes in patients who underwent radical cystectomy: A multicenter retrospective study.
Authors: Naoki Fujita, Masaki Momota, Shingo Hatakeyama, Hiroyuki Ito, Takahiro Yoneyama, Yasuhiro Hashimoto, Kazuaki Yoshikawa, Chikara Ohyama
Journal: Journal of Clinical Oncology (2023)

573 Background: Neoadjuvant chemotherapy (NAC)-induced acute kidney injury (AKI) is a frequent complication in patients with muscle-invasive bladder cancer (MIBC). Although previous studies have reported that AKI during cancer treatment was associated with poor oncological outcomes in several cancers, the impact of NAC-induced AKI on oncological outcomes in patients with MIBC remains unclear. Methods: This retrospective study included 398 patients who received 2-4 cycles of NAC followed by radical cystectomy (RC). AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed AKI during NAC (AKI group) and patients who did not (non-AKI group). Multivariable Cox-proportional hazards regression analyses were performed to evaluate the impact of NAC-induced AKI on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: The median age and follow-up period were 69 years and 62 months, respectively. Of the 398 patients, 66 (17%) developed AKI during NAC. The rates of &lt;ypT2 and downstage in the AKI group were significantly lower than those in the non-AKI group (38% vs. 53%, P = 0.023; 53% vs. 69%, P = 0.013; respectively). After adjustment for age, performance status, cisplatin-based regimen, tumor grade, pathological T stage, pathological lymph-node involvement, and positive surgical margin, AKI was associated with shorter RFS (hazard ratio [HR] 1.619, P = 0.043), CSS (HR 1.727, P = 0.049), and OS (HR 1.848, P = 0.008). Conclusions: NAC-induced AKI was associated with reduced effects of NAC and poor oncological outcomes in patients who underwent RC.
An evaluation of current practice patterns for patients with renal cell carcinoma.
Authors: Leigh Boehmer, Laura S. Wood, Jocelyn Mohs, Andrea Ines Liatis, Wendy Vogel, Maria Matta, Latha Shivakumar
Journal: Journal of Clinical Oncology (2023)

655 Background: First-line immunotherapy and tyrosine kinase inhibitor (TKI) treatment combinations have significantly improved clinical outcomes for patients with renal cell carcinoma (RCC). To maximize clinical benefit of these regimens, risk stratification should guide treatment selection and treatment-related adverse events (AEs) should be appropriately managed. The goal of this project was to identify current practice patterns regarding treatment selection, guideline-based management of AEs, care coordination, and patient education for individuals with RCC treated in community oncology programs and practices. Methods: In July-September 2022, ACCC administered an online survey to evaluate current practice patterns for patients with RCC treated in community cancer programs. To maximize participant engagement, the survey was also shared with advanced practitioner, pharmacist, and oncology nurse members of the Advanced Practitioner Society for Hematology and Oncology (APSHO) and the Kidney Cancer Association who provide care to patients with RCC. Results: Respondents (n=104) were mainly surveyed from community cancer care programs or private/physician practices (69%) in urban/suburban settings (90%) who average 25-75 patients with RCC annually (77%). Most respondents (89%) reported using a combination of an immunotherapeutic and a TKI as initial treatment for advanced clear cell RCC while only 61% of respondents reported frequently using risk scores for newly diagnosed patients. 45% of regimen-specific patient education happens as a separate visit, usually conducted by the oncologist (23%) or the infusion nurse (22%), and 37% of respondents conduct this education on the first day of treatment. The responsibility of providing comprehensive patient education seems to vary by program with the oncologist being the most reported (23%), followed by infusion nurse (22%), clinic nurse (20%), advanced practice provider (18%), and pharmacist (16%). The frequency of monitoring AEs differed based on the given regimen. Respondents mainly (54%) monitored on day 1 of the cycle and again mid-cycle in patients receiving immunotherapy, while 40% monitor only on day 1 of the cycle in patients receiving single-agent TKIs. Clinic nurses are primarily responsible (40%) for monitoring treatment adherence in patients receiving TKIs and also triage for associated AEs. Conclusions: This survey has identified real-world practice patterns related to the management and monitoring of patients with RCC prescribed immunotherapy and tyrosine kinase inhibitor combinations. Opportunities exist to increase utilization of risk assessments, create patient education materials for the multidisciplinary cancer care team, and address the optimal frequency of adverse event monitoring.
Management disparities in metastatic castrate-sensitive prostate cancer (mCSPC).
Authors: Nataliya Mar, Dalia Kaakour
Journal: Journal of Clinical Oncology (2023)

79 Background: Recent approvals in management of high-volume mCSPC offer major improvements in patient outcomes. Triplet therapy combining androgen deprivation therapy (ADT) with docetaxel (D) and novel hormonal therapy (NHT) is the new standard of care in this patient population. Patients ineligible for triplet therapy should receive doublet therapy with ADT plus D or NHT based on category 1 evidence. Multiple retrospective datasets examining the “real-world” mCSPC treatment landscape note significant underutilization of therapies beyond ADT and discordance with treatment guidelines. Methods: A 15-question survey to assess management patterns was electronically distributed to various mCSPC providers in California and Washington. Results: A total of 40 responses were received, with 62.5% identifying as medical oncologists (MO), 20.0% as urologists, 5.0% as radiation oncologists, and 12.5% as advanced practitioners/other. Out of physician responders, 48.6% were academic and 51.4% were community-based. When treating newly diagnosed fit mCSPC patients, 20.0% would prescribe triplet therapy, 42.5% ADT/NHT, 5.0% ADT/D, 5.0% ADT/bicalutamide, 0% ADT alone, 10.0% other therapies, and 17.5% would refer out for therapies beyond ADT. When comparing academic versus community oncologists, 66.7% versus 0% would prescribe triplet therapy, while 22.2% versus 68.8% would prescribe ADT/NHT. Some perceived barriers to following mCSPC treatment guidelines included difficulty keeping up with rapidly evolving data/too many treatment options in 27.5%, insurance coverage concerns in 22.5%, difficulty obtaining early referrals for these therapies in 12.5%, patient factors in 10.0%, and toxicity concerns in 2.5%. When making referrals to MO, 37.5% of non-MO responders would do so at development of mCSPC and 6.3% at mCRPC. Conversely, 24.2% of MO perceived receiving referrals at development of mCSPC and 33.3% at mCRPC. Patterns of ordering genomic testing are listed, with biggest perceived barriers being cost, inadequate access to sequencing platforms and genetic counselors, lack of confidence in counseling about results, and patient refusal. Upon progression from mCSPC to mCRPC, ordering of repeat tumor biopsies would occur “sometimes” by 40.0% of providers, “rarely” by 20.0%, and “never” by 20.0%. Conclusions: Multiple provider disparities when managing mCSPC patients still exist. Our survey demonstrated higher compliance with treatment guidelines than in previous retrospective datasets, possibly due to higher proportion of academic providers. Increased provider awareness of genomic testing recommendations is also needed. [Table: see text]
Cascade genetic testing (CGT) female first-degree relatives (FDR) of men with germline <i>BRCA2 </i>mutations (g<i>BRCA2</i>mut) and prostate cancer (PCa): A cost-effectiveness analysis.
Authors: Alexie A Carletti, Aaron B Caughey, Alexandra Sokolova
Journal: Journal of Clinical Oncology (2023)

110 Background: g BRCA2mut are associated with increased risk of PCa, breast cancer (BC), and ovarian cancer (OC). ~5% of men with metastatic PCa have g BRCA2mut. CGT is recommended for their relatives as there are implications for cancer prevention and early detection strategies. Little is known about CGT initiated by men with PCa. Here we evaluate the cost-effectiveness of CGT in FDR of men with PCa and g BRCA2mut. Methods: A decision-analytic model was created with TreeAge software to compare BC and OC outcomes for female FDRs who underwent CGT for g BRCA2mut versus no CGT. Our theoretical cohort contained 100,000 females, a conservative estimate of patients who could benefit from CGT. We used literature derived estimates to determine the percentage of patients that would pursue risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, both surgeries, or surveillance after CGT. Outcomes included BC or OC diagnoses, survivorship, and cancer death. We derived all probabilities, costs, utilities, and life expectancies from the literature and discounted quality adjusted life years (QALYs) at a rate of 3%. Incremental cost-effectiveness (ICER) was calculated to determine the cost per QALY gained and set the willingness-to-pay threshold at $100,000/QALY. We assessed the robustness of the model with sensitivity analyses. Results: In our theoretical cohort, CGT of female FDRs resulted in 12,910 less BC diagnoses and 6,360 less BC deaths. CGT was associated with lower BC death rates (26.1%) compared to no CGT (35.8%). CGT was not associated with reduction in OC diagnoses or deaths. Our model resulted in lower costs and higher QALYs (a dominant strategy) among the CGT cohort with an ICER of -$4,190.10 per QALY, saving an estimated $595 million. We found that CGT in females was the dominant strategy in 100% of the samples, once uncertainty was incorporated into our model inputs via Monte Carlo simulation. The cost-effectiveness of CGT for male FDRs will be presented at the meeting. Conclusions: In this study, CGT of female FDRs of men with PCa and g BRCA2mut was the dominant strategy to improve BC outcomes, including increased survivorship and reduced BC development. Despite a lack of demonstrated benefit for OC, CGT was associated with reduced costs and increased QALYs. CGT for female FDRs of patients with PCa and g BRCA2mut may be a cost-effective approach for identifying and informing individuals with potentially harmful mutations. [Table: see text]
Effects of baseline C-reactive protein on prognosis in patients with metastatic non-clear cell renal cell carcinoma treated with systemic therapy.
Authors: Ryuichi Mizuno, Yota Yasumizu, Nobuyuki Tanaka, Kazuhiro Matsumoto, Mototsugu Oya
Journal: Journal of Clinical Oncology (2023)

680 Background: With the induction of targeted agents and immune checkpoint inhibitors, treatment strategies for systemic treatment of metastatic renal cell carcinoma (mRCC) have been changed with improved survival. However, those agents were approved based on phase 3 study results designed for clear cell mRCC. For patients with non-clear cell mRCC, those drugs designed for clear cell mRCC have also been used because no validated systemic therapy exists. This retrospective study aimed to identify patients with non-clear cell mRCC who benefit from systemic therapy. Methods: A total of 255 patients with mRCC were reviewed (Institutional review board approval No 2013-0425). Among them, 41 patients who pathologically diagnosed as non-clear cell mRCC and received systemic therapy were retrospectively analyzed. Clinical and pathological data were retrieved and analyzed retrospectively. The prognostic effect of each variable on progression free survival (PFS) and overall survival (OS) were investigated. OS for patients with non-clear cell mRCC was further investigated with univariate and multivariate Cox’s proportional hazards regression models. Results: After a median follow-up of 33.9 months after first line treatment initiation, the median PFS was 3.3 and 19.7 months for non-clear cell and clear cell RCC, respectively (p&lt;0.0001). The median OS was 20.9 and 50.1 months for non-clear cell and clear cell RCC, respectively (p&lt;0.0001). For patients with non-clear cell RCC, univariate analyses revealed duration of first line treatment, baseline C-reactive protein, and International Metastatic RCC Database Consortium (IMDC) risk group (favorable vs intermediate/poor) were significantly correlated with OS, respectively. Multivariate analysis revealed that the duration of first line treatment (HR: 0.997, p=0.027) and the baseline C-reactive protein (HR:1.128, p=0.004) were independent predictors for longer OS in non-clear cell mRCC patients. Conclusions: Systemic therapy for non-clear cell mRCC patients resulted in relatively shorter PFS and OS. A shorter duration of first line treatment and elevated baseline C-reactive protein are correlated with longer OS.
Clinical outcomes after utilization of PSMA PET scans in patients with biochemical recurrent prostate cancer.
Authors: Irene Tsung, Stephen Hynes, Urvashi Mitbander Joshi, Krystal A Morales, Robert Timothy Dess, William C. Jackson, Jeremy MG Taylor, Zachery R Reichert
Journal: Journal of Clinical Oncology (2023)

57 Background: The optimal management of biochemical recurrent prostate cancer (BCR) remains unknown. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans can visualize micrometastatic disease, thus expanding treatment options for BCR from observation or androgen deprivation therapy (ADT) to potentially include metastasis-directed radiation (XRT) or next-generation hormonal agents (NHA). We aimed to describe how BCR patients were managed after PSMA PET scans and their clinical outcomes. Methods: We performed a retrospective chart review of 262 patients from the University of Michigan’s PSMA PET scan database (825 patients with scans 2017–2021). Patients who received maximal local therapy (defined as XRT alone n=199 or surgery + XRT n=63) are presented. Only patients with BCR and a minimum of 1 year follow-up after scans were included. Baseline patient and tumor characteristics, PSMA PET scan results, first and subsequent therapy delivered after PSMA PET, and prostate-specific antigen (PSA) and standard imaging results post PSMA PET were annotated. Primary endpoint is time from first post-scan therapy (within 6 months of scan) to subsequent therapy. Secondary outcomes include probability of no subsequent therapy in 1 year based on first post-scan therapy and PSMA scan findings and PSMA PET findings and association with Gleason score, PSA at BCR, and time from diagnosis to PSMA scan. Results: Of 262 patients with maximal local therapy, 115 met inclusion criteria. Primary definitive treatment was XRT alone in 58% and surgery + XRT in 42%. Median PSA at time of scan was 4.4 ng/mL, and PSMA PET was positive in 87%. First therapy rendered after PSMA PET included 15% no therapy, 26% XRT only, 28% systemic therapy only (ADT +/- NHA), 27% combination therapy (XRT +/- systemic), and 4% other. Subsequent therapy was given in 26%. The median time from first to subsequent therapy was 41 months in patients who received XRT alone as first therapy and not reached for those with combination XRT + ADT. None of the 33 treated with combination therapy required subsequent therapy in 1 year. Remainder of analyses incomplete due to small sample sizes. Results to be updated by time of symposium. Conclusions: This observational study characterizes longer term clinical outcomes in patients with BCR who undergo various therapies after PSMA PET scans. Data may inform current decision making while prospective clinical trial data is awaited.
Effect of race-free estimated glomerular filtration rate equations (eGFR) on oncology clinical trial eligibility for Black patients.
Authors: Benjamin Schmeusser, Arnold Raul Palacios, Eric Midenberg, Reza Nabavizadeh, Dattatraya H Patil, R. Donald Harvey, Janetta Bryksin, Michael J. Connor, Kenneth Ogan, Mehmet Asim Bilen, Viraj A. Master
Journal: Journal of Clinical Oncology (2023)

611 Background: Race is no longer recommended in estimated glomerular filtration rate (eGFR) equations. The resulting lower eGFR may positively impact black patients, such as with earlier nephrology referral. However, the impact of race-free equations on black oncology patients–a cohort more likely to experience inferior cancer outcomes and underrepresentation in clinical trials–has not been fully examined. Here, we analyze removal of race from eGFR in black patients with cancer, specifically with regards to clinical trial eligibility. Methods: Self-identified black patients undergoing nephrectomy at a referral center from 2009-2021 were identified. Patients with end-stage renal disease were excluded. Using preoperative creatinine, height, and weight, eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation with and without race (CKD-EPI-WithRace; CKD-EPI-WithoutRace, respectively), and the Modification of Diet in Renal Disease equation with and without race (MDRD-WithRace; MDRD-WithoutRace, respectively). Distribution of patients and changes within CKD stages with different equations was considered. Theoretical exclusion at commonly observed clinical trial eGFR points was then simulated based on utilization of the race coefficient. Subgroup analysis was completed on patients with stage III-IV disease only. Results: 459 self-identified black patients that underwent nephrectomy at our institution were identified, 135 of which had stage III-IV disease. On average, eGFR decreased around 10-13ml/min/1.73m2 with removal of the race coefficient (Table). 13-22%, 6-12%, and 2-3% more black patients would fall under common clinical trial cutoffs of 60, 45, or 30ml/min cutoffs, respectively, depending on the equation used (Table). Subanalysis of stage III-IV patients only were similar. Conclusions: Race free renal function equations may inadvertently result in increased exclusion of black patients from clinical trials. [Table: see text]
Long-term taxane exposure and transdifferentiation of prostate cancer in vitro.
Authors: Gunhild Von Amsberg, Sergey Dyshlovoy, Jessica Hauschild, Verena Sailer, Sven Perner, Anne Offermann, Lina Merkens, Christoph Krisp, Stefan Werner, Klaus Pantel, Moritz Kaune, Derya Tilki, Hartmut Schlüter, Markus Graefen, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2023)

254 Background: Development of aggressive variants of metastatic castration-resistant prostate cancer (AVPC) is a major challenge in the course of therapy but the underlying mechanisms of aggressive transdifferentiation are not completely understood and appropriate tumor models are missing. Here, we investigated the consequences of long-term taxane exposure on hormone-independent, BRCA2-mutated, AR-V7-positive 22Rv1 cells. Methods: 22Rv1 cells were treated with stepwise increased taxane concentrations for 10 months. Individual clones were picked and further cultured in media containing either docetaxel (Doce) or cabazitaxel (Caba). Passage-matched cells were maintained in culture without treatment. Further characterization was carried out using proliferation, migration, metabolic, and colony formation assays as well as proteomics, RNAseq analyses and xenotransplantation in immunodeficient mice. Results: In total, three single cell 22Rv1-DR clones (50-100-fold resistance to Doce) and three 22Rv1-CR clones (80-150-fold resistance to Caba) were successfully established. All clones showed cross-resistance to either drug. Expectedly, treatment-induced overexpression of ABCB1 was detected and validated. Moreover, alteration of drug resistance related SLC7A5, SLC3A2, and SLC25A24 genes was observed. Additionally, an enrichment analyses identified, among others, neuroendocrine transdifferentiation (GO-term “Neuroendocrine tumors”, p=4.46e-5) to be stimulated in prostate 22Rv1 cells under long-term treatment with Doce or Caba. In line with this, the neuroendocrine features were validated in vitro as well as in xenotransplanted tumors in vivo with upregulation of synaptophysin, chromogranin and neuron specific enolase accompanied by downregulation of the androgen receptor (AR) and upregulation of AR spice variants. Additionally, neuritic morphology, shift to higher nuclear-plasma ratio, partial loss of adherent properties and growth slowdown, along with higher migratory activity were detected. Conclusions: Long-term taxane exposure of 22Rv1 cells resulted in the development of neuroendocrine traits in individual cell clones that have successfully been translated into stable cell lines. Thus, we provide a new cell line model for secondary therapy-induced neuroendocrine transdifferentiation. Further in-depth analysis to identify individual alterations in the course of therapy is currently ongoing.